Case Report Oral Candidiasis in Patients with Level CD4 + Below 50

Approximately 90% of individuals diagnosed with HIV/AIDS have encountered Oral Candidiasis during the progression of their disease, especially in patients with a reduced CD4 + 200 mm 3 . Oral Candidiasis is a prevalent opportunistic infection of the oral cavity. Reported a case of a patient with oral candidiasis in an HIV/AIDS with CD4 + below 50 and discussed the mechanism of molecular relationship decreasing count CD4 + with virulence of Candida Albicans. In this report, we present a case of a 35-year-old female who presented with oral candidiasis. The patient's CD4 + count test revealed a level below 50 and HIV test I-II-III reactive. Human immunodeficiency Virus causes a decrease in CD4 + count and leads to opportunistic oral candidiasis infection.


INTRODUCTION
Oral candidiasis is an opportunistic infection primarily impacting the oral mucosa. 1 The predominant causative agent of these lesions is Candida albicans (C.albicans), a pathogenic organism derived from the normal commensal flora. 2 Candidiasis primarily impacts individuals who are in the vulnerable stages of life, including the very young, the elderly, and those who are immunocompromised due to severe illness. 1 Oral candidiasis, a prevalent form of mucocutaneous candidiasis, is frequently observed in individuals infected with Human Immunodeficiency Virus (HIV)/ Acquired Immune Deficiency Syndrome (AIDS) on a global scale. 3pproximately 90% of people who have HIV/AIDS have encountered oral candidiasis throughout their illness. 3atients with oral candidiasis have elevated viral load and decreased levels of CD4+ T paracardial pneumonia in Sinistra.Sars -Cov 2 PCR resulted in negative.Anti-HIV reagents I, II, and III results were reactive, and the CD4+ count was below 50 because the CD4+ count is so low that the exact amount cannot be detected.
Intra-oral examination in the first visit showed that a thick pseudo membrane, whitish color, in the lower and upper labial mucosa, palate durum and molle, and tongue can be scrapped and left erythema base and felt pain (Figure 1).The pseudo membrane was scrapped and subjected to microbial culture and direct examination.No other lesion was found in the oral cavity.
The oral lesion was then debridement using normal saline, followed by 0.2% chlorhexidine digluconate 0.2%, and oral nystatin 100.000IU/ml was applied to the entire mouth and lip lesion was applied with borax glycerin.
At the next visit, an intra-oral examination still found pseudomembranes on the palate, and the gingiva thinned (Figure 2).The patient's complaints of pain and thickness were reduced.Debridement using normal saline, followed by chlorhexidine di gluconate 0.2%, and oral nystatin 100.000IU/ml to the entire mouth was continued, and fluconazole injection 2 mg/ml was added.The internist gave ARV therapy consisting of Tenovir 300 mg, Lamivudin 300 mg, and Efavirenz 600 mg.
The blood analysis showed a decrease in hemoglobin, hematocrit, and lymphocytes.Anti-toxoplasma IgG was reactive (537.5 IU/ml).The direct microbial examination of the swab results tongue using Vitex® 2 Compact showed Candida Albicans colonies automatically.By microscopic examination, the KOH staining showed a hifa of Candida (Figure 3).
The diagnosis in this patient was oropharyngeal candidiasis associated with HIV/AIDS due to CD4 + .In this patient, clinically in his oral cavity, white pseudomembrane could be scraped in almost the entire oral cavity, mostly in the palate area to the oropharynx.The patient felt the surface of his oral cavity was rough, thick, and sore.
Informed consent was obtained prior to the preparation of the case report, and the authors endeavored all efforts to ensure anonymity.

DISCUSSION
The CD4 + cell count provides an indicator for evaluating the development of a disease. 5When the count of CD4 + cells falls below 200 cells/mm 3 , individuals become susceptible to several pathogenic mechanisms related to AIDS, leading to an increase in developing secondary infections. 6In our case, the count of CD4 + cells falling below 50 cells/mm 3 (< 5%) signifies the progression to the AIDS very advanced stage.Based on clinical and supporting examination, oropharyngeal candidiasis has occurred.Based on the study, this secondary infection starts to occur at CD4 + counts 200/mm. 3IV has a prolonged influence by targeting the immune system, resulting in its compromised state and impaired functionality. 5,7HIV infection results in decreased levels of CD4 + cells through various methods, including apoptosis of uninfected bystander cells. 8he phenomenon of direct elimination of infected cells through viral death and the eradication of infected CD4+ T cells by CD8+ cytotoxic lymphocytes that can recognize infected cells is observed. 6When the CD4 + T cell count decreases below a certain threshold, the functionality of cellmediated immunity is impaired, leading to an increased susceptibility to opportunistic infections. 5CD4 + cells are responsible for stimulating the release of interleukin-17 (IL-17) in mucosal tissues. 9IL-17 is involved in the maintenance of the structural barrier of the GI tracts and mucosal immunity and is driven by the production of IL-22. 9 Oropharyngeal Candidiasis is an oral manifestation due to very low levels of CD4 cells. 12Based on clinical examination, the appearance of oral CAD can vary, with pseudomembranous candidiasis or thrush being the most commonly observed manifestations. 13Thrush is characterized by white patches on the oral mucosa, tongue, or other anatomical regions of the body. 13he lesions have confluent plaques that bear a resemblance to milk curds. 13these plaques reveal a raw, erythematous, and sporadically bleeding base upon removal. 13ropharyngeal Candidiasis is frequently observed in individuals at advanced stages of HIV infection, commonly known as AIDS. 14This condition can manifest through a range of symptoms, such as white patches on the inner cheeks, tongue, palate, and throat, accompanied by redness or discomfort. 15Additionally, individuals may experience a cottony sensation in the mouth, a diminished sense of taste, pain while eating or swallowing, and cracking and redness at the corners of the mouth.
7][18] The growth of Candida is typically constrained by the human immune system and by the presence of other microorganisms, which engage in competitive interactions. 6C. albicans, the predominant yeast species in the oral cavity, exhibit pleomorphism, displaying several development forms, including rodshaped cells, yeast (blastopore) cells, hyphae or pseudohyphae, and chlamydospores. 19he hyphal morphology is commonly regarded as the invasive state of the fungus, facilitating the ability of C. albicans to breach host barriers and infiltrate deep-seated tissues. 18Many virulence factors modulate the infectivity of Candida. 18The expression of virulence factors in C. albicans is modulated by the processes of adhesion and invasion 20 .These processes are facilitated by ALs3 and Ssa1, genes found in C. albicans. 20ALs3 and Ssa1 interact with E-cadherin and epidermal growth factor receptors (Egfr), which are present in oral epithelial cells. 20he binding of ALs3 and Ssa1 to these receptors induces the endocytosis of C. albicans hyphae. 20he synthesis of secreted aspartic proteinases (Saps), which are hyphaassociated proteins, occurs simultaneously with hyphae formation. 21These Saps are crucial in inducing epithelial cell damage and enhancing fungal virulence 21 .Additionally, they facilitate the recruitment of neutrophils and promote the production of pro-inflammatory cytokines such as IL-1ß and TNF-α. 21ue to the severity of the AIDS stage, 2-layer therapy oropharyngeal candidiasis is given to prevent the infection from getting worse.In the first layer, topical therapy was given as antiseptic chlorhexidine in gluconate, 0.2%, and antifungal oral nystatin, 100,000 IU/ml.The second layer of systemic therapy is fluconazole injection at 2 mg/ml.
Chlorhexidine digluconate is a type of antifungal agent that falls under bisbiguanade antimicrobials. 22It is frequently utilized in its gluconate formulation.
Chlorhexidine is an antimicrobial agent with a wide range of effectiveness against gram-positive and gram-negative bacteria, yeast, fungus, protozoa, algae, and viruses. 22Antifungal agents exert their action by disrupting the permeability of cell wall membranes and extracellular proteins, specifically in C. albicans fungi. 23he chlorhexidine formula is often the preferred choice, consisting of a biguanide substitution (N1, N5) attached to hexamethylene, with two chlorophenol rings positioned at either terminus. 22At lower concentrations, chlorhexidine disrupts cellular transport, leading to the creation of holes in the cellular membrane, which subsequently results in damage to fungal cells. 22Chlorhexidine digluconate at a concentration of 0.2% has antiseptic properties, effectively targeting bacteria and fungi. 22The efficacy of a 0.2% chlorhexidine digluconate solution in inhibiting the development of microorganisms, particularly Candida albicans, has been demonstrated through empirical evidence. 22Additionally, this solution has exhibited a notable inhibitory effect on many fungal species, as evidenced by a substantial zone of inhibition. 23,22he classification of anti-fungal therapy encompasses three distinct categories: The three classes of compounds discussed are polyenes, azoles, and pyrimidines.1 Nystatin is classified as a polyene antifungal agent, which exerts its mechanism of action by selectively attaching to sterol structures present in the cell membranes of fungi, particularly ergosterol.24 This binding event leads to a notable elevation in cell permeability, resulting in the leaking of intracellular molecules.7

CONCLUSION
The oral lesions associated with HIV were commonly considered significant indicators and markers of HIV/AIDS.The Decrease in CD4 + in HIV/AIDS condition also decreased the amount of IL-17 and IL-22, which were cytokines that induced the secretion of local innate immunity cells in the oral cavity (ß-Defensin, S100A8/A9, and Histatin) which in turn led to susceptibility of the oral mucosa epithelium and provided a suitable environment for the transformation of C. albicans from commensal microbiome to pathogenic.

ACKNOWLEDGMENT
We would like to thank the Head and Ethics Committee of Dr. Ramelan Naval Hospital Surabaya-Indonesia for consent to take and collect data for this case report.

Figure 1 .Figure 2 .Figure 3 .
Figure 1.The oral mucosa in the patient with pseudomembranous dorsum of the tongue (A) and palate (B)